Flat cellular revertants which are resistant to transformation by ras and certain other oncogenes have been described. Resistance to transformation can be demonstrated both by cell fusion of revertant cells to transformed cells or by direct infection with transforming retroviruses. Resistance of the revertants to transformation is specific -- ras, fes, and src-related oncogenes do not transform the revertant cells efficiently, while cells transformed by a number of other oncogenic agents including the retroviral oncogenes fms, sis and mos, SV40, polyoma, and a number of chemically transformed cell lines retain their transformed phenotype after fusion. Revertant cells secrete a transforming growth factor into their culture medium which is capable of inducing NIH/3T3 and NRK test cells to grow in semisolid agar. Revertants do not respond to exogenous transforming growth factors, indicating that the revertant phenotype may be due to a cellular alteration affecting the function of TGF or some later stage in the biochemical pathway leading to cell transformation. Initial studies indicate that the revertant phenotype is transmissible to recipient cells by DNA transfection procedures, an indication that it may be possible to identify the molecular basis for reversion. Finally, 2 transformation-sensitive proteins, which are present in normal NIH/3T3 cells, disappear in transformed cells, and reappear in the revertant cell lines, have been detected in 2-dimensional gel electrophoresis studies.